A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies
- Conditions
- B-cell MalignancyRelapsed CancerRefractory CancerB-cell Lymphoma
- Interventions
- Registration Number
- NCT06634589
- Lead Sponsor
- BeiGene
- Brief Summary
The purpose of this study is to measure the safety, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics with BGB-16673 in combination with other agents in participants with relapsed or refractory (R/R) B-cell malignancies. This study is structured as a master protocol with separate substudies. This study currently includes four substudies, and more substudies may be added as other combination agents are identified.
- Detailed Description
This new study will check how safe and helpful a potential anticancer drug called BGB-16673 is in participants with R/R B-cell malignancies when it is given in combination with other medicines - sonrotoclax in substudy 1, zanubrutinib in substudy 2, mosunetuzumab in substudy 3, and glofitamab in substudy 4.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
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Must sign the informed consent form (ICF) and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the ICF
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Confirmed diagnosis of a R/R B-cell malignancy
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Protocol-defined measurable disease
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Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
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Adequate organ function
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Female participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for 30 days after the last dose of BGB-16673 or zanubrutinib, 60 days after the last dose of glofitamab, or 90 days after the last dose of sonrotoclax or mosunetuzumab. A negative urine or serum pregnancy test result must be provided 10-14 days before the first dose of study treatment
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Nonsterile male participants must be willing to use a highly effective method of birth control and refrain from sperm donation for the duration of the study and for 30 days after the last dose of BGB-16673 or zanubrutinib, 60 days after the last dose of glofitamab, or 90 days after the last dose of sonrotoclax or mosunetuzumab
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Substudies 1, 3, and 4 Inclusion Criterion:
- Adequate renal function as indicated by estimated glomerular filtration rate (eGFR) of ≥ 50 mL/min
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Substudy 2 Inclusion Criteria:
- Bruton tyrosine kinase (BTK) inhibitor-naive, or previously received treatment with a covalent BTK inhibitor and discontinued for reasons other than clinical progression
- Adequate renal function as indicated by eGFR of ≥ 30 mL/min
Key
-
Treatment-naive B-cell malignancies
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Unable to comply with the requirements of the protocol
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Active leptomeningeal disease or uncontrolled, untreated brain metastasis
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Any malignancy ≤ 2 years before first dose of study treatment except for the specific cancer under investigation in this study or any locally recurring cancer that has been treated curatively
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Autologous stem cell transplant ≤ 3 months prior to screening or chimeric antigen T-cell therapy ≤ 3 months prior to screening
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Substudies 1 and 2: Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or who have taken calcineurin inhibitors within 4 weeks prior to consent
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Participants who have a history of severe allergic reactions or hypersensitivity to the active ingredient and excipients of BGB-16673, sonrotoclax, zanubrutinib, mosunetuzumab, or glofitamab
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Substudy 1 Exclusion Criterion:
- Prior treatment with a B-cell lymphoma-2 (Bcl-2) inhibitor (with exception for participants who relapsed ≥ 24 months after completion of a full course of a prior Bcl-2 inhibitor containing regimen)
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Substudy 2 Exclusion Criterion:
- Participants who discontinued prior zanubrutinib treatment due to intolerance
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Substudies 3 and 4 Exclusion Criteria:
- Prior exposure to a CD20 x CD3 T-cell engager antibody treatment
- All participants with a prior allogeneic stem cell transplant
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 1 Part 1a: Dose Escalation BGB-16673 Sequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies. Substudy 1 Part 1a: Dose Escalation Sonrotoclax Sequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies. Substudy 1 Part 1b: Safety Expansion BGB-16673 Cohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies. Substudy 1 Part 1b: Safety Expansion Sonrotoclax Cohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies. Substudy 2 Part 1a: Dose Escalation BGB-16673 Sequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies. Substudy 2 Part 1a: Dose Escalation Zanubrutinib Sequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies. Substudy 2 Part 1b: Safety Expansion BGB-16673 Cohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies. Substudy 2 Part 1b: Safety Expansion Zanubrutinib Cohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies. Substudy 3 Part 1a: Dose Escalation BGB-16673 Sequential cohorts of increasing dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies. Substudy 3 Part 1a: Dose Escalation Mosunetuzumab Sequential cohorts of increasing dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies. Substudy 3 Part 1b: Safety Expansion BGB-16673 Cohorts of select dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies. Substudy 3 Part 1b: Safety Expansion Mosunetuzumab Cohorts of select dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies. Substudy 4 Part 1a: Dose Escalation BGB-16673 Sequential cohorts of increasing dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies. Participants will receive obinutuzumab as pretreatment prior to the start of combination treatment. Substudy 4 Part 1a: Dose Escalation Glofitamab Sequential cohorts of increasing dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies. Participants will receive obinutuzumab as pretreatment prior to the start of combination treatment. Substudy 4 Part 1a: Dose Escalation Obinutuzumab Sequential cohorts of increasing dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies. Participants will receive obinutuzumab as pretreatment prior to the start of combination treatment. Substudy 4 Part 1b: Safety Expansion BGB-16673 Cohorts of select dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies. Substudy 4 Part 1b: Safety Expansion Glofitamab Cohorts of select dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies. Substudy 4 Part 1b: Safety Expansion Obinutuzumab Cohorts of select dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies.
- Primary Outcome Measures
Name Time Method Substudy 3 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years] Substudy 4 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 4 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 1 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 1 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 2 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 2 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years Substudy 3 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
- Secondary Outcome Measures
Name Time Method Substudy 1 Parts 1a and 1b: Overall Response Rate (ORR) in participants with B-cell malignancies Up to approximately 3 years ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by investigator.
Substudy 1 Parts 1a and 1b: Time to Response (TTR) Up to approximately 3 years TTR is defined as the time from treatment initiation to first documented response.
Substudy 1 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 1 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 1 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 1 Part 1a: Terminal half-life (t1/2) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 2 Parts 1a and 1b: ORR in participants with B-cell malignancies Up to approximately 3 years ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator.
Substudy 1 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and sonrotoclax From Week 1 to Week 17 Substudy 2 Parts 1a and 1b: TTR Up to approximately 3 years TTR is defined as the time from treatment initiation to the first documented response.
Substudy 2 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and zanubrutinib From Week 1 to Week 17 Substudy 2 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and zanubrutinib From Week 1 to Week 17 Substudy 2 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and zanubrutinib From Week 1 to Week 17 Substudy 3 Parts 1a and 1b: DOR Up to approximately 3 years DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.
Substudy 3 Parts 1a and 1b: TTR Up to approximately 3 years TTR is defined as the time from treatment initiation to the first documented response.
Substudy 3 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and mosunetuzumab From Week 1 to Week 12 Substudy 3 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and mosunetuzumab From Week 1 to Week 12 Substudy 3 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and mosunetuzumab From Week 1 to Week 12 Substudy 3 Part 1a: Terminal half-life (t1/2) of BGB-16673 and mosunetuzumab From Week 1 to Week 12 Substudy 3 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and mosunetuzumab From Week 1 to Week 36 Substudy 4 Parts 1a and 1b: ORR in participants with B-cell malignancies Up to approximately 3 years ORR is defined as the percentage of participants with partial response (PR) or better as assessed by the investigator.
Substudy 4 Parts 1a and 1b: DOR Up to approximately 3 years DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.
Substudy 4 Parts 1a and 1b: TTR Up to approximately 3 years TTR is defined as the time from treatment initiation to the first documented response.
Substudy 4 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 From Week 1 to Week 10 Substudy 4 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 From Week 1 to Week 10 Substudy 4 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 From Week 1 to Week 10 Substudy 4 Part 1a: Terminal half-life (t1/2) of BGB-16673 From Week 1 to Week 10 Substudy 4 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 From Week 1 to Week 10 Substudy 1 Parts 1a and 1b: Duration of Response (DOR) Up to approximately 3 years DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.
Substudy 2 Part 1a: Terminal half-life (t1/2) of BGB-16673 and zanubrutinib From Week 1 to Week 17 Substudy 2 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and zanubrutinib From Week 1 to Week 17 for Part 1a; From Week 1 to Week 5 for Part 1b Substudy 1 Part 1b: Number of patients with complete response or complete response with incomplete count recovery (CR/CRi) who achieve undetectable minimal residual disease (uMRD) Up to approximately 3 years Substudy 3 Parts 1a and 1b: ORR in participants with B-cell malignancies Up to approximately 3 years ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator.
Substudy 2 Parts 1a and 1b: DOR Up to approximately 3 years DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.
Related Research Topics
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Trial Locations
- Locations (49)
Hospital Sirio Libanes Brasilia
🇧🇷Brasilia, Brazil
Ensino E Terapia de Inovacao Clinica Amo Etica
🇧🇷Salvador, Brazil
Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
🇧🇷Sao Jose Do Rio Preto, Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
🇧🇷Sao Paulo, Brazil
Mayo Clinic Phoenix
🇺🇸Phoenix, Arizona, United States
University of Southern Californianorris Comprehensive
🇺🇸Los Angeles, California, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
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